Cinnoline N-oxides

Dinitrobiphenyl, in an alkaline solution, is reduced to benzo[c]cinnoline N-oxide (Scheme 83) [122,123]. 

Dinitrobiphenyl (57)44 88 is thus reducible in alkaline solution at a suitable potential to benzo[c]cinnoline N-oxide (58) in acid solution the reduction proceeds to 4,5-dihydrobenzo[c]cinnoline (59) which is very easily oxidized, e.g., by air, to benzo[c]cinnoline (60). 

N-oxides can also be reduced. For example, the microbial deoxygenation of a series of aromatic and heteroaromatic N-oxide compounds, including quinoline N-oxides, isoquinoline N-oxides, 2-aryl-2H-benzotriazole 1-oxides, benzo[c]cinnoline N-oxide and azoxybenzene, has performed with bakers yeast-NaOH to afford quinolines and pyridines (291l... 

A number of reports on transition metal-free formations of benzo [c] cinnolines emerged in 2014. Sythana and collaborators prepared benzo [c] cinnoline N-oxides via a single-electron transfer mechanism (Scheme 11) (14EJ0311). In the presence of potassium tert.-butoxide and an aptotic nonpolar solvent benzo [c] cinnoline N-oxides 18 were obtained in moderate-to-high yields from the reaction of substituted anilines with nitrobenzenes. Both electron-donating substituents and electron-withdrawing halo substituents were well tolerated. When the halo substituents were in the... 

By controlling the potential the reaction can be stopped at the N-oxide stage at more negative potentials the reduction can be controlled to give either benzo[c]cinnoline or its dihydro derivative. 

The photodecomposition of benzotriazine N-oxides produced 3-substituted 2,1-benzisoxazoles (Scheme 183) (73JA2390). The photolysis of cinnoline 1-oxides produced 3-methyl-2,1-benzisoxazoles (Scheme 183) (74TL2643,74T2645). 

N-Oxidation of cinnoline (2) with hydrogen peroxide in acetic acid results in the formation of four products cinnoline 1-oxide (92 26%), cinnoline 2-oxide (93 50%), cinnoline... 

Durr et al. have described some novel complex cinnoline derivatives which show photochromic properties. Albini et al. have provided some new evidence on the mechanism for the photoisomerization of heterocyclic N-oxides. Simple pyridine N-oxides are exceptional. Thus irradiation of pyridine N -oxide in aqueous base affords the ring-opened product (23). Aoyama et al. have described the unprecedented photocyclization of the amide (24) to the lactam (25). The first examples of C2a+2Tr] photoreactions of a three-membered ring and an azo-compound have been described by Hunig and Schmitt. Nicolaou et al. have prepared the first stable example of a 1,2-dithiethane the procedure involves (2i +2Tr) photodimerization of C=S groups. 

Oxidations of 2,2 -diaminobiphenyls with sodium perborate, phenyl iodosodiacetate, ° or manganese dioxide have given benzo[c]cinnolines with hydrogen peroxide in acetic acid, cyclization is accompanied by N-oxidation. These reactions, which parallel the oxidation of arylamines... 

The benzo[c]cinnoline ring system is resistant to oxidation by chromic acid, but is oxidized to pyridazinetetracarboxylic acid by alkaline permanganate. " Benzo[c]cinnoline has been oxidized to the 5-oxide with hydrogen peroxide in acetic acid at 0°C, and further to the 5,6-dioxide at 110°-120 C. The JV-oxidation of various other derivatives has been reported, although the main method for the preparation of N-oxides has been by the reduction of 2,2 -dinitrobiphenyls (Section II,A,2). In the case of unsymmetrically substituted compounds, both of the above methods usually give mixtures of 5- and 6-oxides. Selectivity is occasionally observed, thus 4-bromobenzo[c]cinnoline is oxidized to the 6-oxide, presumably owing to steric factors. Benzo[c]cinnoline oxides of known orientation have been obtained by the cyclization of 2-amino-2 -nitro-biphenyl derivatives (Section II,A,2). 

JV,JV -Dioxides or IV-oxides may be formed as intermediates in these reactions, depending on the stage at which N—N bond formation takes place (Scheme 1) and on the vigor of the subsequent reduction. By suitable choice of reaction conditions these may be isolated for example, reduction of 2,2 -dinitrobiphenyl with sodium hydrosulfide gives high yields of benzo[c]-cinnoline 5-oxide (5),11 while catalytic hydrogenation in solutions containing sodium hydroxide can be stopped at the 5,6-dioxide (4), or carried further.151618... 

Benzo[c]cinnoline-5,6-dioxide is a colorless, high-melting (243°C), non-basic compound, sparingly soluble in organic solvents. There has been discussion of spectroscopic evidence as to whether it has a di-N-oxide or a nitroso-dimer type structure,12,137,138 but there has been little investigation of its chemistry and there appears to be no chemical evidence for its behaving as 2,2 -dinitrosobiphenyl i.e., it shows no nitroso group reactions. 

The past year has seen the publication of Comprehensive Organic Chemistry, one volume of which contains much information on the six-membered ring systems to be reviewed in this article a monograph on the chemistry of condensed pyrazines has also appeared. Reviews on 1,4-thiazines, l,3-benzothiazines," pyridazines, benzo[c]cinnolines, quinazolines, purines, pyrrolo[3,2-c]quino-lines, 1,10-phenanthroline and its complexes, polyaza-phenanthrenes, and 1,9- and 1,10-diaza-anthracenes have been published. Other specialist reviews are devoted to catalytic methods of obtaining pyridine bases pyridine N-oxides the stereochemistry of quinolizines, indolizines, and pyrrolizines benzothiazinone dioxides 2-quinazolones and their cyclic homologues (e.g. 

Note Cinnoline A(-oxides may be prepared directly by primary synthesis (see Chapter 1) or by N-oxidation of an existing cinnoline with a peroxy reagent, as exemplified here. 

Cinnoline 2-oxide (113) underwent deoxidative cine-amination with primary or secondary amines to afford, for example, 3-propylaminocinnoline (114, R = NHPr) (neat PrNH2, reflux, 25 h 53%) or 3-(pyrrolidin-l-yl)cinnoline [114, R = N(CH2)4] [HN(CH2)4, reflux, 60 h > 95%]. ... 

A typical example of the cme-amination is interaction of cinnoline-2-oxide with an excess of primary or secondary amines, producing 3-aminocinnolines in 26-98% yields (Scheme 47) [105]. The lowest yield corresponds to the most bulky isopropylamine. It is evident that the reaction proceeds via the intermediate adduct 71 followed by its aromatization with elimination of water. Interestingly, the reaction of cinnoline-2-oxide with propylamine or pyrrolidine, which takes place in the presence of AgPy2Mn04, also affords the corresponding 3-aminocinnolines as the only products in 60 and 95% yields, respectively. Thus, even under oxidative conditions the cine-substitution pathway prevails on the oxidative amination. At the same time, as it has been already mentioned in Sect. 3.2 (Scheme 29), pyrimido-pyridazine A(2)-oxide 46 is aminated in the presence of AgPy2Mn04 both with loss of the N-oxide function and with its retention. 

Thus, a new route for the Beirut reaction is revealed in which a number of novel 2-amino-3-(2-nitrophenyl)quinoxalines, in addition to their expected 1,4-dioxides, can be easily prepared and converted into novel quinoxalino[2,3-c]cinnoline 5-N-oxide which are rare in literature. In these investigations the curious fact is the fortuitous finding that the methyl substituents of some of quinoxalino[2,3-c]cin-nolines, or their presumed 5-Af-oxides intermediates, can be easily converted into acetals or orthoesters which we believe to be unprecedented. 

This has been observed with dialkylaminoazobenzenes N-oxides, that, when irradiated in IIM sulfuric acid, cyclize to the corresponding benzo[c]cinnoline, theN-oxide group in this case serving as an oxidant of the dihydrobenzophenanthrene intermediate. ... 

This method is exemplified by its application to quinoline, isoquinoline, cinnoline, and isoquinoline 2-oxide, which are nitrated as their conjugate acids. The rate profiles for these compounds and their N- or O-methyl perchlorates show closely parallel dependences upon acidity (fig. 2.4). Quaternisation had in each case only a small effect upon the rate, making the criterion a very reliable one. It has the additional advantage of being applicable at any temperature for which kinetic measurements can be made (table 8.1, sections B and D). 

Oxidative photocyclization of benzylideneaniline appears to proceed efficiently only in the presence of strong acid. The phenanthridine 31, however, has been prepared by irradiation of the imine 3228 few other examples of the photocyclization of arylimines have been reported.29 Strong acid is also required for successful photocyclization of azobenzenes to benzo-[c]cinnolines. Here, protonation is claimed to lower the reactive n, n excited state below the level of the unreactive n, it state. 2-Phenylazopyridine,... 

Quinoline 1-oxides can be rearranged photochemically into indoles (103 — 104 — 105) or N-hydroxyindoles (106 — 107). Cinnolines are reductively ring-contracted into indoles (Section 3.2.1.6.9.ii). 

Benzo[c]cinnoline derivatives of different oxidation levels are prepared by N-N bond formations from suitable 2,2 -disubstituted biphenyls as outlined in Scheme 5. 

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